Inconsistency of Classical Penalized Likelihood Approaches under Endogeneity

With the high speed development of information technology, contemporary data from a variety of fields becomes extremely large. The number of features in many datasets is well above the sample size and is called high dimensional data. In statistics, variable selection approaches are required to extract the efficacious information from high dimensional data. The most popular approach is to add a penalty function coupled with a tuning parameter to the log likelihood function, which is called penalized likelihood method. However, almost all of penalized likelihood approaches only consider noise accumulation and supurious correlation whereas ignoring the endogeneity which also appeared frequently in high dimensional space. In this paper, we explore the cause of endogeneity and its influence on penalized likelihood approaches. Simulations based on five classical pe-nalized approaches are provided to vindicate their inconsistency under endogeneity. The results show that the positive selection rate of all five approaches increased gradually but the false selection rate does not consistently decrease when endogenous variables exist, that is, they do not satisfy the selection consistency.

Exploring influential factors and endogeneity of traffic flow of different lanes on urban freeways using Bayesian multivariate spatial models

The traffic flow pertinent modelling is essential for distinct strategy formulations.However,the present literature illustrated some needed improvements for such models,especially those related to lane-specific flow.Given such context,this study aims to bridge the research gap by generating regression models to investigate influential factors for traffic flow based on the data collected from one multilane freeway.With the Full Bayesian specification,the hierarchical models were built by accounting for three types of random effects:the structured and unstructured spatial effects,and the one addressing the multivariate heterogeneity across multiple lanes.The endogenous relationship of traffic flow of adjacent lanes was also explored by utilizing the capability of multivariate correlation structure for simultaneous estimation of lane flow.The model estimates revealed the presence of endogeneity with statistical significance for the flow of neighbouring lanes for both directions of travel.The impact of flow was not only limited to the adjacent lanes but also to non-adjacent lanes.The multivariate specification also confirmed interdependency for lane flows.Compared to conventional approaches,the more accurate model estimation in the study indicates the advantage of incorporating the various correlation structures in the models.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Exploration of the contributing factors to the walking and biking travel frequency using multi-level joint models with endogeneity

The enormous advantages of active transportation lead the transportation research focus towards enhancing the walking and biking trips.The present study explored the influential factors to the walking and biking travel frequency based on data obtained from the National Household Travel Survey California add-on survey.The study features some highlights.First,bivariate models were used to account for the common unobserved heterogeneity shared at both household and personal levels.Second,endogeneity was explicitly considered.Third,both variable importance ranking and correlation analysis are employed to determine the different features to be fed into each of the joint models.The results illustrated that the models developed with endogeneity performed better than the models without endogeneity.Four influential variables which includes mode to work by bicycle,public transit usage,count of household members,and multiple race responses,tend to have statistically significant impacts on walking and biking trips.

Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

Strain-dependent alpha-synuclein spreading in Parkinson's disease and multiple system atrophy

Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) aggregates.These a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble aggregates.Oligomeric forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.

Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.

Elucidation of potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa

Dry-cured meat products are considerably popular around the world due to unique flavor.Proteolysis is one of the enzymatic reactions from which flavor substances are derived,which is affected by endogenous proteases.The purpose aimed to reveal the potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa in this paper.The dynamic changes of endogenous proteases activity,free amino acids,and volatiles during dry-cured pork coppa processing were characterized.The results showed that 5 kinds of free amino acids,Glu,Lys,Val,Ala,and Leu,were identified as significant contributors to taste.Meanwhile,key volatiles,such as hexanal,nonanal,octanal,benzaldehyde,3-methyl butanoic acid,2-methyl propanoic acid,and ethyl octanoate,greatly contributed to the flavor characteristics of dry-cured pork coppa.Further partial correlation analysis was performed to better elucidate the relationship among parameters.The results revealed that close relationship between endogenous proteases and key substances.RAP not only significantly affected the accumulation of key active-amino acids,but also affected the accumulation of ethyl octanoate,2,3-pentanedione,and 2,3-octanedione by regulating the accumulation of octanoic acid and Leu.In addition,cathepsin B and D,DPP II,DPP IV and RAP notably affected accumulation of hexanal.

A core scientific problem in the treatment of central nervous system diseases:newborn neurons

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.

Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice

Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in neoplasia.However,the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma(HCC)remain dismal.AIM To establish a cyclin dependent kinase inhibitor 2A(CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC.METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database.Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples.The targeted microRNAs were predicted by lncBasev3.0,and the targeted mRNAs were predicted by miRDB,and Targetscan database.The univariate and multivariate analysis were utilized to identify independent prognostic indicators.RESULTS CDKN2A was frequently mutated and deleted in HCC.The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways.The CDKN2A-related ceRNA network-growth arrest specific 5(GAS5)/miR-25-3p/SRY-box transcription factor 11(SOX11)was successfully established.GAS5 was recognized as an independent prognostic biomarker,whose overexpression was correlated with a poor prognosis in HCC patients.The association between GAS5 expression and methylation,immune infilt-ration was explored.Besides,traditional Chinese medicine effective components targeting GAS5 were obtained.CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression.Moreover,GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

A New Regime Switching Model with State-Varying Endogeneity

In this paper,we propose a state-varying endogenous regime switching model(the SERS model),which includes the endogenous regime switching model by Chang et al.,the CCP model,as a special case.To estimate the unknown parameters in the SERS model,we propose a maximum likelihood estimation method.Monte Carlo simulation results show that in the absence of state-varying endogeneity,the SERS model and the CCP model perform similarly,while in the presence of state-varying endogeneity,the SERS model performs much better than the CCP model.Finally,we use the SERS model to analyze Chinese stock market returns,and our empirical results show that there exists strongly state-varying endogeneity in volatility switching for the Shanghai Composite Index returns.Moreover,the SERS model can indeed produce a much more realistic assessment for the regime switching process than the one obtained by the CCP model.

Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p

BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.

Research on the Design of Rural Cultural Tourism Space under the Background of Rural Revitalization: A Case Study of Dujiazhuang Village, Mentougou, Beijing

From the perspective of endogenous development concept,Dujiazhuang Village,Mentougou was taken as an example to explore the development of rural cultural tourism space.The rural tourism resources in the west of Beijing are rich in type and numerous,but the development of cultural tourism is unbalanced and inadequate.Guided by the endogenousconcept and driven by the design of cultural tourism space,rural public space should be as the entry point to integrate the elements of rural resources and create a design that stimulates the endogenous ability of villagers.Culture can promote tourism,and industry can drive the economy to increase income and enhance the villagers'cultural identity.

Cytoplasmic DNA: sources, sensing, and role in aging and disease

Endogenous cytoplasmic DNA(cytoDNA)species are emerging as key mediators of inflammation in diverse physiological and pathological contexts.Although the role of endogenous cytoDNA in innate immune activation is well established,the cytoDNA species themselves are often poorly characterized and difficult to distinguish,and their mechanisms of formation,scope of function and contribution to disease are incompletely understood.

Cytoplasmic DNA:sources,sensing,and role in aging and disease

Endogenous cytoplasmic DNA(cytoDNA)species are emerging as key mediators of inflammation in diverse physiological and pathological contexts.Although the role of endogenous cytoDNA in innate immune activation is well established,the cytoDNA species themselves are often poorly characterized and difficult to distinguish,and their mechanisms of formation,scope of function and contribution to disease are incompletely understood.Here,we summarize current knowledge in this rapidly progressing field with emphases on similarities and differences between distinct cytoDNAs,their underlying molecular mechanisms of formation and function,interactions between cytoDNA pathways,and therapeutic opportunities in the treatment of age-associated diseases.

Principles for Designing New Types of Housing for a Strong and Resilient Local Economy in the Republic of Congo

The Congolese population is organised into households, which are thus headed by a chief who ensures the social well-being, development and integration into working life of the individuals in his charge. This study examines the functional principles of new housing design as an instrument for transforming the (current) failing economy into a strong and resilient one. Accordingly, a literature review of the practice of designing and building housing in human settlements in the Congo revealed the state of the art on this subject. An analysis of the existing housing stock from a demographic, social and economic point of view made it possible to identify the most common household sizes and numbers, as well as the lifestyle processes that determine the need for developed space. To this end, the experimental method was used to propose configuration plans for various new types of dwelling. To this end, the study highlighted the link between people’s standard of living and the effectiveness of their involvement in the local economy. To achieve the aims of the National Development Plan (NDP), particular attention must be paid to solving the housing problem. The existing housing stock actively contributes to the problems associated with unemployment and insecurity. Functional principles for the design of new types of housing have been developed. Four model types are proposed in line with the demographic structure of the population, their socio-economic characteristics and their lifestyle.

An Endogenous Feedback and Entropy Analysis in Machine Learning Model for Stock’s Return Forecast

Stock markets exhibit Brownian movement with random,non-linear,uncertain,evolutionary,non-parametric,nebulous,chaotic characteristics and dynamism with a high degree of complexity.Developing an algorithm to predict returns for decision-making is a challenging goal.In addition,the choice of vari-ables that will serve as input to the model represents a non-triviality,since it is possible to observe endogeneity problems between the predictor and the predicted variables.Thus,the goal is to analyze the endogenous origin of the stock return prediction model based on technical indicators.For this,we structure a feed-for-ward neural network.We evaluate the endogenous feedback between the pre-dicted returns and technical analysis indicators based on the generated residues.It is possible to predict the return.The high accuracy of the model indicates that,during the test period,there is a hit rate close to 76%.Regarding endogeneity,the term of interest and the return are the variables that influence the largest number of indicators.The results will help investors build investment strategies based on this expert system applied to forecasting.

The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

Advances on genetic and genomic studies of ALV resistance

Avian leukosis(AL)is a general term for a variety of neoplastic diseases in avian caused by avian leukosis virus(ALV).No vaccine or drug is currently available for the disease.Therefore,the disease can result in severe economic losses in poultry flocks.Increasing the resistance of poultry to ALV may be one effective strategy.In this review,we provide an overview of the roles of genes associated with ALV infection in the poultry genome,including endogenous retroviruses,virus receptors,interferon-stimulated genes,and other immune-related genes.Furthermore,some methods and techniques that can improve ALV resistance in poultry are discussed.The objectives are willing to provide some valuable references for disease resistance breeding in poultry.